The antihemophilic factor (AHF) is a high molecular weight glycoprotein which functions as a regulatory protein in the intrinsic mechanism of blood coagulation. The high carbohydrate content (20%) of the AHF suggests that the carbohydrate may play a significant role in the structure and function of the AHF. This project is a study of the structure of the AHF molecule, especially the carbohydrate portion of the AHF, and of the physiological function of the carbohydrate on the AHF. The AHF molecule can be cleaved to smaller fragments with plasmin and trypsin, and the pieces studied individually. Investigations are being made on the composition of the carbohydrate, the number, types and partial sequences of the carbohydrate chains, and the nature of the glycopeptide linkages. The role of the carbohydrate will be investigated by sequentially cleaving off certain of the sugar moieties with specific glycosidases and comparing the treated AHF to native AHF in terms of its 3- dimensional structure, in vitro and in vivo activity, ability to bind Factor IXa, turnover in vivo, and immunological activity. These studies should provide a greater understanding not only of the basic structure and function of AHF, but also of the basis of its immunological activity and the reasons for its rapid turnover in vivo. These findings could be important not only in the treatment of hemophilia, but also for the management of certain hypercoagulable states.